Using frozen section to identify histological patterns in stage I lung adenocarcinoma of ≤ 3 cm: accuracy and interobserver agreement

Abstract

Aims: The IASLC/ATS/ERS classification of lung adenocarcinoma provides a prognostically significant histological subclassification. The aim of this study was to investigate the accuracy, limitations and interobserver agreement of frozen sections for predicting histological subtype.

Methods and results: Frozen section and permanent section slides from 361 resected stage I lung adenocarcinomas ≤ 3 cm in size were reviewed for predominant histological subtype and the presence or absence of lepidic, acinar, papillary, micropapillary and solid patterns. Fifty cases were additionally reviewed by three pathologists to determine interobserver agreement. To test the accuracy of frozen section in judging degree of invasion, five pathologists reviewed frozen section slides from 35 cases with a predominantly lepidic pattern. There was moderate agreement on predominant histological subtype between frozen sections and final diagnosis (κ = 0.565). Frozen sections had high specificity for micropapillary and solid patterns (94% and 96%, respectively), but sensitivity was low (37% and 69%, respectively). The interobserver agreement was satisfactory (κ > 0.6, except for the acinar pattern).

Conclusions: Frozen section can provide information on the presence of aggressive histological patterns-micropapillary and solid-with high specificity but low sensitivity. It was difficult to predict the predominant pattern on the basis of frozen sections, mostly because of sampling issues.

Keywords: frozen sections; histological subtype; invasion; limited resection; lung adenocarcinoma; micropapillary; solid.

Figure 1

Patient selection tree. Among the 1540 patients with lung adenocarcinoma who underwent surgical resection from 1995 to 2009, intraoperative frozen section was performed on tumors from 821 patients. Among these patients, 692 had stage I disease with tumor size ≤3 cm. The original frozen section slides were available for 379 patients. Among these patients, we excluded 17 cases of invasive mucinous adenocarcinoma and 1 case of colloid adenocarcinoma. The remaining 361 cases constituted the study cohort. FS, frozen section; MSKCC, Memorial Sloan-Kettering Cancer Center.

Figure 2

Morphologic profile of histologic patterns in good-quality frozen section slides and the corresponding frozen section control slides. Lepidic pattern (A, B), acinar pattern (C, D), papillary pattern (E, F), micropapillary pattern (G, H), and solid pattern (I, J) in frozen section and frozen section control slides, respectively. Hematoxylin and eosin stain; original magnification × 200.

Figure 3

Morphologic profile of histologic patterns in poor-quality frozen section slides and the corresponding frozen section control slides. Lepidic pattern (A, B), acinar pattern (C, D), papillary pattern (E, F), micropapillary pattern (G, H), and solid pattern (I, J) in frozen section and frozen section control slides, respectively. Hematoxylin and eosin stain; original magnification × 200.

Figure 4

Kaplan-Meier curves for time to all types of recurrence stratified by predominant histologic subtype, and presence or absence of micropapillary or solid pattern in permanent sections and frozen sections.

Figure 5

Kaplan-Meier curves for time to locoregional recurrence stratified by predominant histologic subtype, and presence or absence of micropapillary or solid pattern in permanent sections and frozen sections.

Figure 6

Kaplan-Meier curves for time to distant recurrence stratified by predominant histologic subtype, and presence or absence of micropapillary or solid pattern in permanent sections and frozen sections.

Figure 7

An example of a case in which the frozen section inflation method was applied. The alveolar spaces are well expanded, and the area of invasive growth (marked by “+”) could be easily distinguished from the surrounding, noninvasive area (marked by “*”).